title: Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination.
abstract: Methylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are widely misused psychoactive drugs. Methylphenidate increases brain dopamine and norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA releases serotonin, dopamine and norepinephrine through the same transporters. Pharmacodynamic interactions of methylphenidate and MDMA are likely. This study compared the pharmacodynamic and pharmacokinetic effects of methylphenidate and MDMA administered alone or in combination in healthy subjects using a double-blind, placebo-controlled, crossover design. Methylphenidate did not enhance the psychotropic effects of MDMA, although it produced psychostimulant effects on its own. The haemodynamic and adverse effects of co-administration of methylphenidate and MDMA were significantly higher compared with MDMA or methylphenidate alone. Methylphenidate did not change the pharmacokinetics of MDMA and vice versa. Methylphenidate and MDMA shared some subjective amphetamine-type effects; however, 125 mg of MDMA increased positive mood more than 60 mg of methylphenidate, and methylphenidate enhanced activity and concentration more than MDMA. Methylphenidate and MDMA differentially altered facial emotion recognition. Methylphenidate enhanced the recognition of sad and fearful faces, whereas MDMA reduced the recognition of negative emotions. Additionally, the present study found acute pharmacodynamic tolerance to MDMA but not methylphenidate. In conclusion, the combined use of methylphenidate and MDMA does not produce more psychoactive effects compared with either drug alone, but potentially enhances cardiovascular and adverse effects. The findings may be of clinical importance for assessing the risks of combined psychostimulant misuse. Trial registration identification number: NCT01465685 (http://clinicaltrials.gov/ct2/show/NCT01465685).
authors.affiliation: Psychopharmacology Research Group, Division of Clinical Pharmacology and Toxicology, Departments of Biomedicine and Internal Medicine, University Hospital and University of Basel, Switzerland.
authors.forename: Cédric M
authors.initials: CM
authors.lastname: Hysek
authors.affiliation: Psychopharmacology Research Group, Division of Clinical Pharmacology and Toxicology, Departments of Biomedicine and Internal Medicine, University Hospital and University of Basel, Switzerland.
authors.forename: Linda D
authors.initials: LD
authors.lastname: Simmler
authors.affiliation: Psychopharmacology Research Group, Division of Clinical Pharmacology and Toxicology, Departments of Biomedicine and Internal Medicine, University Hospital and University of Basel, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schillinger
authors.affiliation: Psychopharmacology Research Group, Division of Clinical Pharmacology and Toxicology, Departments of Biomedicine and Internal Medicine, University Hospital and University of Basel, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Meyer
authors.affiliation: Psychopharmacology Research Group, Division of Clinical Pharmacology and Toxicology, Departments of Biomedicine and Internal Medicine, University Hospital and University of Basel, Switzerland.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Schmid
authors.affiliation: Psychopharmacology Research Group, Division of Clinical Pharmacology and Toxicology, Departments of Biomedicine and Internal Medicine, University Hospital and University of Basel, Switzerland.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Donzelli
authors.affiliation: Biomedicine Service, University Hospital Lausanne, Lausanne, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Grouzmann
authors.affiliation: Psychopharmacology Research Group, Division of Clinical Pharmacology and Toxicology, Departments of Biomedicine and Internal Medicine, University Hospital and University of Basel, Switzerland.
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Liechti
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D019540:Area Under Curve; D001341:Autonomic Nervous System / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D004703:Endocrine System / Q000187:drug effects; D005260:Female; D006213:Hallucinogens / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000097:blood / Q000494:pharmacology*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000097:blood / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D004338:Drug Combinations; D006213:Hallucinogens; D008774:Methylphenidate; D018817:N-Methyl-3,4-methylenedioxyamphetamine